Injectable sustained release formulations offer the opportunity to provide therapeutic amounts of active pharmaceutical ingredients over an extended period of time from a single injection, thus eliminating the need for once or twice daily injections. Presently available injectable sustained release formulations utilizing, for example, microspheres and an aqueous carrier, carry several disadvantages. The formulations do not offer long term stability in the aqueous carrier, thus necessitating separate packaging and storage for the microspheres and aqueous carrier, and the patient must take several steps to combine the microspheres and aqueous carrier before administering the injection.
Another disadvantage of presently available injectable microsphere formulations is a large burst release following injection, which causes an undesirable in vivo release of active pharmaceutical ingredient in a single burst. When medications have toxic or deleterious side effects, this is undesirable.
There is a need for formulations and methods of safely administering sustained release pharmaceutical formulations to patients so that the active ingredient will be released in vivo over an extended period of time and without an unacceptable initial burst release. Ideally the active ingredient is released so as to maintain levels within the therapeutic window, i.e., in the concentration range above that needed to cause the desired clinical effect, but below that where undesirable side effects outweigh the benefits of the drug. It is also necessary that this active pharmaceutical ingredient be provided in a manner that is easy and convenient for the patient to self-administer and that is provided in a formulation that maintains stability for a long period of time in a liquid state. The disclosure is directed to these as well as other important ends.